Initial methotrexate monotherapy supported for early RA

medwireNews: Patients with early rheumatoid arthritis (RA) who receive initial treatment with methotrexate monotherapy followed by second-line adalimumab have comparable long-term clinical outcomes to those given first-line methotrexate plus adalimumab, researchers report.

These data “fully validate” the current treat-to-target strategy advocated by the ACR and EULAR guidelines, which recommend starting with methotrexate monotherapy, followed by escalation to biologic treatment “[i]f disease activity has not improved at 3 months, or the clinical target is not attained within 6 months and the patient has unfavourable prognostic markers,” say Arthur Kavanaugh (University of California at San Diego, La Jolla, USA) and study co-authors.

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The team conducted a post-hoc analysis of the OPTIMA study, the primary results of which demonstrated that 26 weeks of treatment with first-line methotrexate plus adalimumab resulted in significantly more patients achieving low disease activity (LDA) – defined as a Disease Activity Score at 28 joints based on C-reactive protein (DAS28-CRP) of less than 3.2 points – compared with methotrexate alone.

After week 26, methotrexate-treated patients who achieved LDA continued with the same treatment, whereas those in the combination arm were randomly assigned to continue with dual therapy or to receive methotrexate alone. Among patients who did not achieve LDA, those in the adalimumab plus methotrexate group continued to receive combination therapy, while those in the methotrexate monotherapy group were given open-label adalimumab rescue therapy in addition to methotrexate from week 26 onwards.

The post-hoc analysis, reported in the Annals of the Rheumatic Diseases, categorized patients into those who received methotrexate plus adalimumab throughout the study, and those initially given methotrexate monotherapy.

“These two main groupings allowed comparison of the validity of the EULAR and ACR recommendations,” explain Kavanaugh et al.

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At the 1-year follow-up, 65% of 465 patients initially given methotrexate plus adalimumab and 62% of 460 patients given first-line methotrexate monotherapy achieved LDA, a nonsignificant difference. Similarly, 65% of patients in both groups achieved LDA at week 78, and a comparable proportion of patients in both groups had normal function – defined as a Health Assessment Questionnaire Disability Index (HAQ-DI) score of less than 0.5 points.

However, a significantly higher proportion of patients in the first-line combination therapy group had no radiographic progression – defined as a change in modified total Sharp/van der Heijde score from baseline of no more than 0.5 points – at the 1-year and 78-week follow-up visits, with rates of 86% versus 72% for the initial methotrexate group at both timepoints.

Although these results suggest that initial combination therapy gives rise to “minimally superior radiographic outcomes at a group level compared with initial [methotrexate] monotherapy,” the researchers note that the proportion of patients with no radiographic progression remained stable after week 26, “indicating that as soon as adalimumab rescue therapy began […], progression of joint damage stopped.”

And the researchers conclude: “Consistent with current treatment recommendations, starting with [methotrexate] monotherapy and optimising treatment by adding adalimumab after treatment failure at 26 weeks allowed patients with early RA to achieve comparable long-term clinical, functional and disease activity outcomes with patients who started with initial adalimumab [combination therapy].”